Comparing Isocitrate Dehydrogenase Inhibitors with Procarbazine, Lomustine, and Vincristine Chemotherapy for Oligodendrogliomas

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The abstract has been submitted for presentation to the AANS 2026 meeting being held in San Antonio, TX, USA. Introduction: Oligodendrogliomas are an uncommon subset of gliomas that are molecularly defined by 1p/19q codeletion in the setting of an isocitrate dehydrogenase (IDH) 1/2 mutation. Standard-of-care management involves maximal safe resection followed by adjuvant chemoradiation with procarbazine, lomustine, and vincristine (PCV). Although PCV confers a durable survival advantage, treatment-limiting toxicity is common and often necessitates discontinuation. IDH inhibitors such as vorasidenib have demonstrated promising efficacy and more favorable tolerability profiles, but a paucity of comparative data across therapeutic classes limits optimal treatment decision-making. Methods: A systematic search was conducted through to 7 March 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Eligible studies included adult patients (≥18 years) with IDH-mutant, 1p/19q-codeleted oligodendrogliomas treated with PCV chemotherapy or IDH inhibitors and with a minimum follow-up of 12 months. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events (AEs) that led to treatment discontinuation. Results: Twenty-eight studies met the inclusion criteria, with a total of 406 patients. All 406 patients carried a confirmed diagnosis of oligodendroglioma. For mixed-histology cohorts, only oligodendroglioma-specific data were extracted and analyzed. Among PCV cohorts, median PFS ranged from 24.3 months to 8.4 years and median OS was reported up to 14.7 years in long-term follow-up from RTOG 9402 and EORTC 26951. Grade ≥ 3 AEs resulted in treatment discontinuation in 65–70% of patients, primarily due to hematologic or neurologic events. In comparison, vorasidenib achieved a median PFS of 27.7 months in the phase III INDIGO trial (HR 0.39; 95% CI 0.27–0.56; p < 0.001), with median OS not yet reached at 14.2 months of follow-up. Grade ≥ 3 AEs occurred in 22.8% of patients and led to treatment discontinuation in only 1–3%, primarily due to asymptomatic transaminitis. Early real-world data from expanded-access programs similarly support these tolerability findings. Conclusions: While PCV chemotherapy remains the standard-of-care systemic therapy for oligodendroglioma supported by mature survival data, IDH inhibitors represent a mechanistically targeted alternative with encouraging early-phase outcomes and a significantly improved safety profile. Direct comparison across these regimens is constrained by differences in study design and limited long-term OS data for IDH inhibitors. Prospective head-to-head trials are essential for defining the optimal therapeutic sequence in this evolving treatment landscape. In the interim, we provide a recommend approach for current use.

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